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Protein

F-actin-uncapping protein LRRC16A

Gene

CARMIL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:19846667).2 Publications

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

GO - Biological processi

  • actin filament network formation Source: UniProtKB
  • actin filament organization Source: BHF-UCL
  • barbed-end actin filament uncapping Source: UniProtKB
  • blood coagulation Source: Reactome
  • cell migration Source: BHF-UCL
  • lamellipodium assembly Source: BHF-UCL
  • macropinocytosis Source: UniProtKB
  • negative regulation of barbed-end actin filament capping Source: UniProtKB
  • positive regulation of actin filament polymerization Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of lamellipodium organization Source: UniProtKB
  • positive regulation of stress fiber assembly Source: UniProtKB
  • positive regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
  • ruffle organization Source: BHF-UCL
  • urate metabolic process Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-983231. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
F-actin-uncapping protein LRRC16ACurated
Alternative name(s):
CARMIL homologBy similarity
Capping protein regulator and myosin 1 linker protein 1Imported
Capping protein, Arp2/3 and myosin-I linker homolog 1By similarity
Capping protein, Arp2/3 and myosin-I linker protein 11 Publication
Leucine-rich repeat-containing protein 16AImported
Gene namesi
Name:CARMIL11 PublicationImported
Synonyms:CARMILBy similarity, LRRC16, LRRC16A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:21581. CARMIL1.

Subcellular locationi

GO - Cellular componenti

  • cell leading edge Source: UniProtKB
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • filamentous actin Source: UniProtKB
  • lamellipodium Source: BHF-UCL
  • macropinosome Source: UniProtKB
  • nucleus Source: HPA
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi55604.
OpenTargetsiENSG00000079691.
PharmGKBiPA162394368.

Polymorphism and mutation databases

BioMutaiLRRC16A.
DMDMi74762279.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003258151 – 1371F-actin-uncapping protein LRRC16AAdd BLAST1371

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei122PhosphoserineCombined sources1
Modified residuei916PhosphothreonineCombined sources1
Modified residuei968PhosphoserineCombined sources1
Modified residuei1067PhosphoserineCombined sources1
Modified residuei1094PhosphoserineCombined sources1
Modified residuei1228PhosphothreonineCombined sources1
Modified residuei1280PhosphoserineCombined sources1
Modified residuei1288PhosphoserineCombined sources1
Modified residuei1291PhosphoserineCombined sources1
Modified residuei1315PhosphoserineCombined sources1
Modified residuei1324PhosphoserineCombined sources1
Modified residuei1331PhosphoserineCombined sources1
Modified residuei1360PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ5VZK9.
MaxQBiQ5VZK9.
PaxDbiQ5VZK9.
PeptideAtlasiQ5VZK9.
PRIDEiQ5VZK9.

PTM databases

iPTMnetiQ5VZK9.
PhosphoSitePlusiQ5VZK9.

Expressioni

Tissue specificityi

Expressed in lung, placenta, small intestine, liver, thymus, colon, skeletal muscle, heart and brain. Higher expression in kidney.1 Publication

Gene expression databases

BgeeiENSG00000079691.
CleanExiHS_LRRC16A.
ExpressionAtlasiQ5VZK9. baseline and differential.
GenevisibleiQ5VZK9. HS.

Organism-specific databases

HPAiHPA029038.
HPA029039.

Interactioni

Subunit structurei

Homodimer (PubMed:19846667). Interacts (via C-terminus) with heterodimer capping protein (CP); this interaction uncaps barbed ends capped by CP, enhances barbed-end actin polymerization and promotes lamellipodial formation and cell migration (By similarity). Interacts with heterodimer capping protein (CP) (PubMed:19846667). Interacts with MYO1E (PubMed:19846667). Interacts with TRIO (PubMed:19846667).By similarity1 Publication

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120745. 15 interactors.
DIPiDIP-56920N.
IntActiQ5VZK9. 6 interactors.
MINTiMINT-5005073.
STRINGi9606.ENSP00000331983.

Structurei

Secondary structure

11371
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi978 – 980Combined sources3
Helixi985 – 988Combined sources4
Beta strandi999 – 1002Combined sources4
Helixi1026 – 1029Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LK2X-ray2.20T961-1012[»]
3LK3X-ray2.68T964-1078[»]
ProteinModelPortaliQ5VZK9.
SMRiQ5VZK9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5VZK9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati245 – 269LRR 1Add BLAST25
Repeati275 – 298LRR 2Add BLAST24
Repeati304 – 327LRR 3Add BLAST24
Repeati336 – 363LRR 4Add BLAST28
Repeati391 – 418LRR 5Add BLAST28
Repeati423 – 447LRR 6Add BLAST25
Repeati481 – 506LRR 7Add BLAST26
Repeati543 – 566LRR 8Add BLAST24
Repeati570 – 593LRR 9Add BLAST24
Repeati654 – 678LRR 10Add BLAST25
Repeati958 – 981LRR 11Add BLAST24

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni958 – 1082Inhibits capping activity of CAPZA2By similarityAdd BLAST125
Regioni1055 – 1089Necessary for localization at the cell membrane1 PublicationAdd BLAST35

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili710 – 734Sequence analysisAdd BLAST25

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1243 – 1250Poly-Ser8

Domaini

The C-terminus is necessary for localization to the cell membrane (PubMed:26578515).1 Publication

Sequence similaritiesi

Belongs to the CARMIL family.Curated
Contains 11 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Coiled coil, Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4242. Eukaryota.
ENOG410Y5JZ. LUCA.
GeneTreeiENSGT00390000014487.
HOGENOMiHOG000230565.
HOVERGENiHBG108094.
InParanoidiQ5VZK9.
KOiK20493.
OMAiGVDEFFT.
OrthoDBiEOG091G01FI.
PhylomeDBiQ5VZK9.
TreeFamiTF316381.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR029764. CARMIL1.
IPR031943. CARMIL_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
[Graphical view]
PANTHERiPTHR24112:SF39. PTHR24112:SF39. 1 hit.
PfamiPF16000. CARMIL_C. 1 hit.
PF13516. LRR_6. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5VZK9-1) [UniParc]FASTAAdd to basket
Also known as: CARMIL1a1 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTEESSDVPR ELIESIKDVI GRKIKISVKK KVKLEVKGDK VENKVLVLTS
60 70 80 90 100
CRAFLVTARI PTKLELTFSY LEIHGVVCSK SAQMIVETEK CSISMKMASP
110 120 130 140 150
EDVSEVLAHI GTCLRKIFPG LSPVRIMKKV SMEPSERLAS LQALWDSQTV
160 170 180 190 200
AEQGPCGGFS QMYACVCDWL GFSYREEVQW DVDTIYLTQD TRELNLQDFS
210 220 230 240 250
HLDHRDLIPI IAALEYNQWF TKLSSKDLKL STDVCEQILR VVSRSNRLEE
260 270 280 290 300
LVLENAGLRT DFAQKLASAL AHNPNSGLHT INLAGNPLED RGVSSLSIQF
310 320 330 340 350
AKLPKGLKHL NLSKTSLSPK GVNSLSQSLS ANPLTASTLV HLDLSGNVLR
360 370 380 390 400
GDDLSHMYNF LAQPNAIVHL DLSNTECSLD MVCGALLRGC LQYLAVLNLS
410 420 430 440 450
RTVFSHRKGK EVPPSFKQFF SSSLALMHIN LSGTKLSPEP LKALLLGLAC
460 470 480 490 500
NHNLKGVSLD LSNCELRSGG AQVLEGCIAE IHNITSLDIS DNGLESDLST
510 520 530 540 550
LIVWLSKNRS IQHLALGKNF NNMKSKNLTP VLDNLVQMIQ DEESPLQSLS
560 570 580 590 600
LADSKLKTEV TIIINALGSN TSLTKVDISG NGMGDMGAKM LAKALQINTK
610 620 630 640 650
LRTVIWDKNN ITAQGFQDIA VAMEKNYTLR FMPIPMYDAS QALKTNPEKT
660 670 680 690 700
EDALQKIENY LLRNHETRKY LQEQAYRLQQ GIVTSTTQQM IDRICVKVQD
710 720 730 740 750
HLNSLRNCGG DAIQEDLKSA ERLMRDAKNS KTLLPNLYHV GGASWAGASG
760 770 780 790 800
LLSSPIQETL ESMAGEVTRV VDEQLKALLE SMVDAAENLC PNVMKKAHIR
810 820 830 840 850
QDLIHASTEK ISIPRTFVKN VLLEQSGIDI LNKISEVKLT VASFLSDRIV
860 870 880 890 900
DEILDALSHC HHKLADHFSR RGKTLPQQES LEIELAEEKP VKRSIITVEE
910 920 930 940 950
LTEIERLEDL DTCMMTPKSK RKSIHSRMLR PVSRAFEMEF DLDKALEEVP
960 970 980 990 1000
IHIEDPPFPS LRQEKRSSGF ISELPSEEGK KLEHFTKLRP KRNKKQQPTQ
1010 1020 1030 1040 1050
AAVCAANIVS QDGEQNGLMG RVDEGVDEFF TKKVTKMDSK KWSTRGSESH
1060 1070 1080 1090 1100
ELNEGGDEKK KRDSRKSSGF LNLIKSRSKS ERPPTILMTE EPSSPKGAVR
1110 1120 1130 1140 1150
SPPVDCPRKD TKAAEHNGNS ERIEEIKTPD SFEESQGEEI GKVERSDSKS
1160 1170 1180 1190 1200
SPQAGRRYGV QVMGSGLLAE MKAKQEKRAA CAQKKLGNDA VSQDSSSPAL
1210 1220 1230 1240 1250
SGVERSDGGG AVPKLHPGLP ENRFGLGTPE KNTKAEPKAE AGSRSRSSSS
1260 1270 1280 1290 1300
TPTSPKPLLQ SPKPSLAARP VIPQKPRTAS RPDDIPDSPS SPKVALLPPV
1310 1320 1330 1340 1350
LKKVPSDKER DGQSSPQPSP RTFSQEVSRR SWGQQAQEYQ EQKQRSSSKD
1360 1370
GHQGSKSNDS GEEAEKEFIF V
Length:1,371
Mass (Da):151,557
Last modified:December 7, 2004 - v1
Checksum:i6DECD6387FD73DCE
GO
Isoform 2 (identifier: Q5VZK9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1177-1221: Missing.

Note: No experimental confirmation available.
Show »
Length:1,326
Mass (Da):147,088
Checksum:iBC4881025483CA27
GO
Isoform 3 (identifier: Q5VZK9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     486-499: SLDISDNGLESDLS → QLGTRYRNAVLRVY
     500-1371: Missing.

Note: No experimental confirmation available.
Show »
Length:499
Mass (Da):55,117
Checksum:iA77D54FABEE374C8
GO
Isoform 4 (identifier: Q5VZK9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-161: Missing.
     292-337: GVSSLSIQFA...SLSANPLTAS → ETTTKIKRQN...NYYSDFSHDG
     338-1371: Missing.

Note: No experimental confirmation available.
Show »
Length:176
Mass (Da):20,181
Checksum:i806D8D31AAC2A04A
GO

Sequence cautioni

The sequence BAA90912 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti255N → D in BAC85701 (PubMed:14702039).Curated1
Sequence conflicti889K → R in BAA90912 (PubMed:14702039).Curated1
Sequence conflicti1202G → S in ACI49709 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03992377V → I.Corresponds to variant rs9358856dbSNPEnsembl.1
Natural variantiVAR_039924545P → L.Corresponds to variant rs12207840dbSNPEnsembl.1
Natural variantiVAR_039925639A → G.Corresponds to variant rs7454756dbSNPEnsembl.1
Natural variantiVAR_0399261117N → S.Corresponds to variant rs9885914dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0324151 – 161Missing in isoform 4. 1 PublicationAdd BLAST161
Alternative sequenceiVSP_032416292 – 337GVSSL…PLTAS → ETTTKIKRQNVPTVLQTYLV VCPSDYQPCPLPLGKDNYYS DFSHDG in isoform 4. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_032417338 – 1371Missing in isoform 4. 1 PublicationAdd BLAST1034
Alternative sequenceiVSP_032418486 – 499SLDIS…ESDLS → QLGTRYRNAVLRVY in isoform 3. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_032419500 – 1371Missing in isoform 3. 1 PublicationAdd BLAST872
Alternative sequenceiVSP_0324201177 – 1221Missing in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ009082 mRNA. Translation: ACI49709.1.
AK123817 mRNA. Translation: BAC85701.1.
AK125696 mRNA. Translation: BAC86250.1.
AK000055 mRNA. Translation: BAA90912.1. Different initiation.
AL160037, AL022170, AL024509 Genomic DNA. Translation: CAH72024.1.
AL022170, AL024509, AL160037 Genomic DNA. Translation: CAI21583.1.
AL024509, AL022170, AL160037 Genomic DNA. Translation: CAI21665.1.
CCDSiCCDS54973.1. [Q5VZK9-1]
RefSeqiNP_060110.4. NM_017640.5. [Q5VZK9-1]
UniGeneiHs.649550.

Genome annotation databases

EnsembliENST00000329474; ENSP00000331983; ENSG00000079691. [Q5VZK9-1]
GeneIDi55604.
KEGGihsa:55604.
UCSCiuc011djw.2. human. [Q5VZK9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ009082 mRNA. Translation: ACI49709.1.
AK123817 mRNA. Translation: BAC85701.1.
AK125696 mRNA. Translation: BAC86250.1.
AK000055 mRNA. Translation: BAA90912.1. Different initiation.
AL160037, AL022170, AL024509 Genomic DNA. Translation: CAH72024.1.
AL022170, AL024509, AL160037 Genomic DNA. Translation: CAI21583.1.
AL024509, AL022170, AL160037 Genomic DNA. Translation: CAI21665.1.
CCDSiCCDS54973.1. [Q5VZK9-1]
RefSeqiNP_060110.4. NM_017640.5. [Q5VZK9-1]
UniGeneiHs.649550.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LK2X-ray2.20T961-1012[»]
3LK3X-ray2.68T964-1078[»]
ProteinModelPortaliQ5VZK9.
SMRiQ5VZK9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120745. 15 interactors.
DIPiDIP-56920N.
IntActiQ5VZK9. 6 interactors.
MINTiMINT-5005073.
STRINGi9606.ENSP00000331983.

PTM databases

iPTMnetiQ5VZK9.
PhosphoSitePlusiQ5VZK9.

Polymorphism and mutation databases

BioMutaiLRRC16A.
DMDMi74762279.

Proteomic databases

EPDiQ5VZK9.
MaxQBiQ5VZK9.
PaxDbiQ5VZK9.
PeptideAtlasiQ5VZK9.
PRIDEiQ5VZK9.

Protocols and materials databases

DNASUi55604.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329474; ENSP00000331983; ENSG00000079691. [Q5VZK9-1]
GeneIDi55604.
KEGGihsa:55604.
UCSCiuc011djw.2. human. [Q5VZK9-1]

Organism-specific databases

CTDi55604.
DisGeNETi55604.
GeneCardsiLRRC16A.
H-InvDBHIX0005632.
HGNCiHGNC:21581. CARMIL1.
HPAiHPA029038.
HPA029039.
MIMi609593. gene.
neXtProtiNX_Q5VZK9.
OpenTargetsiENSG00000079691.
PharmGKBiPA162394368.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4242. Eukaryota.
ENOG410Y5JZ. LUCA.
GeneTreeiENSGT00390000014487.
HOGENOMiHOG000230565.
HOVERGENiHBG108094.
InParanoidiQ5VZK9.
KOiK20493.
OMAiGVDEFFT.
OrthoDBiEOG091G01FI.
PhylomeDBiQ5VZK9.
TreeFamiTF316381.

Enzyme and pathway databases

ReactomeiR-HSA-983231. Factors involved in megakaryocyte development and platelet production.

Miscellaneous databases

ChiTaRSiLRRC16A. human.
EvolutionaryTraceiQ5VZK9.
GeneWikiiLRRC16A.
GenomeRNAii55604.
PROiQ5VZK9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000079691.
CleanExiHS_LRRC16A.
ExpressionAtlasiQ5VZK9. baseline and differential.
GenevisibleiQ5VZK9. HS.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR029764. CARMIL1.
IPR031943. CARMIL_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
[Graphical view]
PANTHERiPTHR24112:SF39. PTHR24112:SF39. 1 hit.
PfamiPF16000. CARMIL_C. 1 hit.
PF13516. LRR_6. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCARL1_HUMAN
AccessioniPrimary (citable) accession number: Q5VZK9
Secondary accession number(s): B8X1J0
, Q6ZUH5, Q6ZW07, Q9NXU7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 7, 2004
Last modified: November 30, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.